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Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDAapproved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remains largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells after ischemia in both models. rtPA signi cantly reduced Cav-1 expression and increases pCav-1/Cav-1 ratio in bEnd.3 cells, but not in the in vivo model. In addition, we rst show that increased Cav-1 immunoreactivity in the infarcted area and Cav-1 serum levels are positively correlated at 24 h post-MCAO. Interestingly, Cav-1 expression in infarcted area and baseline serum Cav-1 levels negatively correlate with hemorrhagic volume, supporting a protective role of Cav-1 in cerebral ischemia and pointing to a potential usefulness of baseline serum Cav-1 levels as predictor of hemorrhagic volume, independently of rt-PA administration.

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